Published today in Clinical Medicine Insights: Therapeutics is a new original research article by Suman Wason, Jennifer L. DiGiacinto and Matthew W. Davis.  Read more about this paper below:

Title

Clinically Significant Pharmacokinetic Interaction Between Colchicine and Ritonavir in Healthy Volunteers

Abstract

Colchicine is a substrate for cytochrome 3A4 (CYP3A4) enzyme and P-glycoprotein efflux transporter (P-gp); consequently, concomitant administration with drugs that inhibit these have the potential to cause clinically significant increases in colchicine plasma concentrations and precipitate adverse events. Ritonavir, a protease inhibitor, elicits potent CYP3A4 and P-gp inhibitory activity. In this open-label, nonrandomized, one-sequence, two-period study, 24 healthy volunteers received a single 0.6-mg dose of colchicine alone and together with multiple-dose ritonavir (100 mg twice daily for 4 days) to evaluate drug-drug interactions. Serial blood samples were collected for the determination of colchicine plasma concentrations. Standard pharmacokinetic parameter values were calculated along with 90% confidence intervals (ie, area under the concentration-time curve plasma from time zero to the time of last quantifiable concentration [AUC0-t and AUC0-8], maximum drug concentration [Cmax]) for colchicine alone and colchicine combined with multiple-dose ritonavir. The mean Cmax and AUC0-t were significantly increased (170% and 245%, respectively) when colchicine was coadministered with ritonavir as compared with colchicine alone. Study data confirm the need for a dose adjustment (approximately 50% reduction) when colchicine is coadministered with strong CYP3A/P-gp inhibitors.

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